CNR1 and diabetes mellitus: Furthermore, interferon regulatory factor 5 (IRF5) was found to be an essential down-stream mediator of CB1R signaling in macrophages in diabetes (47) and transplantation of CB1R-/- bone marrow to pre-diabetic ZDF rats prevented β-cell loss and diabetic complications, supporting the pathogenic role CB1R-mediated IRF5 signaling.